title: [Regulating effect of N-acetyl-seryl-aspartyl-lysyl-proline on activation of c-jun N-terminal kinase pathway in rats with silicosis].
abstract: OBJECTIVE
  To investigate the regulatory effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the activation of c-jun N-terminal kinase (JNK) signal transduction pathway and its role in silicotic fibrosis.
  
  
  METHODS
  A rat model of silicosis was developed by intratracheal instillation. Sixty rats were randomly divided into 4-week control group (n = 10), 8-week control group (n = 10), 4-week silicosis model group (n = 10), 8-week silicosis model group (n = 10), AcSDKP treatment group (n = 10), and AcSDKP prevention group (n = 10). The content of hydroxyproline in lung tissue was measured using a p-dimethylaminoben-zaldehyde reagent; the expression levels of transforming growth factor (TGF)-beta 1 (TGF-β1), phospho-JNK, JNK, and c-jun in lung tissue were measured by Western blot. The lung fibroblasts from neonatal rats were cultured, and the 4th generation of cells were used in the experiment; these cells were divided into control group, TGF-β1 stimulation group, SP600125 intervention group, and AcSDKP intervention group. The distributions of phospho-JNK and c-jun in lung fibroblasts were observed by immunocytochemistry; the expression levels of type I collagen and type III collagen in lung fibroblasts were measured by Western blot.
  
  
  RESULTS
  The expression levels of TGF-β1, phospho-JNK, and c-jun and the content of hydroxyproline in the AcSDKP treatment group were 70.60%, 78.03%, 79.85%, and 71.28%, respectively, of those in the 4-week silicosis model group (P < 0.05) and 77.99%, 66.73%, 69.94%, and 64.82%, respectively, of those in the 8-week silicosis model group (P < 0.05); the expression levels of TGF-β1, phospho-JNK, and c-jun and the content of hydroxyproline in the AcSDKP prevention group were 84.56%, 61.18%, 64.73%, and 74.96%, respectively, of those in the 8-week silicosis model group (P < 0.05). The expression levels of phospho-JNK and c-jun in the AcSDKP intervention group were 54.59% and 55.56%, respectively, of those in the TGF-β1 stimulation group; the expression levels of type I collagen and type III collagen in the AcSDKP intervention group were 79.9% and 84.4%, respectively, of those in the TGF-β1 stimulation group (P < 0.05).
  
  
  CONCLUSIONS
  AcSDKP exerts anti-silicotic fibrosis effect probably by inhibiting the activation of JNK signal transduction pathway mediated by TGF-β1 and the deposition of interstitial collagen.
authors.affiliation: Department of Pathology, Hebei United University, Tangshan 063000, China.
authors.forename: Zhong-qiu
authors.initials: ZQ
authors.lastname: Wei
authors.forename: Wan-ying
authors.initials: WY
authors.lastname: Yu
authors.forename: Hai-li
authors.initials: HL
authors.lastname: Feng
authors.forename: Wen-dong
authors.initials: WD
authors.lastname: Ma
authors.forename: Zhi-guo
authors.initials: ZG
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Rui-min
authors.initials: RM
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
mesh_terms: D000818:Animals; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D012829:Silicosis / Q000378:metabolism* / Q000473:pathology
chemical_list: D009842:Oligopeptides; D048031:JNK Mitogen-Activated Protein Kinases; C058504:goralatide